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Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif
Abstract
The human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defences by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors; however, the underlying mechanism by which Vif achieves this remains unclear. Here we report a crystal structure of the Vif-CBF-β-CUL5-ELOB-ELOC complex. The structure reveals that Vif, by means of two domains, organizes formation of the pentameric complex by interacting with CBF-β, CUL5 and ELOC. The larger domain (α/β domain) of Vif binds to the same side of CBF-β as RUNX1, indicating that Vif and RUNX1 are exclusive for CBF-β binding. Interactions of the smaller domain (α-domain) of Vif with ELOC and CUL5 are cooperative and mimic those of SOCS2 with the latter two proteins. A unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contacts with the other proteins but stabilizes the conformation of the α-domain, which may be important for Vif-CUL5 interaction. Together, our data reveal the structural basis for Vif hijacking of the CBF-β and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs.
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“For instance, the Vif protein of the human immunodeficiency virus (HIV) hijacks CRL5 and binds the cotranscription factor CBF-b leading to degradation of A3F and A3G, proteins that block viral replication.[95][96][97]”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [96]
In the citing paper
“The Cullin 5 complex is well known for being hijacked by the HIV viral protein Vif 101”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [101]
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Metadata
- Authors
- Guo, Y., Dong, L., Qiu, X., Wang, Y., Zhang, B., Liu, H., Yu, Y., Zang, Y., Yang, M., & Huang, Z.
- Affiliations
- Harbin Institute of Technology (CN)
- Center for Life Sciences (CN)
- Corresponding author
- Huang, Zhiwei
- Venue
- Nature
- Published
- 2014-01
- Volume
- 505
- Issue
- 7482
- Pages
- 229-233
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2049689155
- Cited by
- 202
- References
- 36
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 14 · 2021: 18 · 2020: 18 · 2019: 14 · 2018: 13 · 2017: 21 · 2016: 18 · 2015: 30 · 2014: 28
- FWCI
- 14.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- HIV-1 Vif, CBFβ, CUL5, elongin B, ELOC, E3 ubiquitin ligase, host restriction factors, proteasomal degradation, zinc finger, RUNX1, crystal structure, antiviral drug targets, HIV-1 replication, protein-protein interaction
- MeSH terms
- Elongin, Amino Acid Sequence, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Transcription Factors, Protein Structure, Tertiary, Crystallography, X-Ray, Cullin Proteins, Multiprotein Complexes, Core Binding Factor beta Subunit, Core Binding Factor Alpha 2 Subunit, Suppressor of Cytokine Signaling Proteins, vif Gene Products, Human Immunodeficiency Virus, Protein Stability
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